tbuckley/cabot-search huggingface dataset:
Potential new solution to reduce skin complications and improve quality of life in people living with a stoma
Journal: British Journal of Dermatology (2023)

Journal Article Potential new solution to reduce skin complications and improve quality of life in people living with a stoma Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Page e28, https://doi.org/10.1093/bjd/ljad049 Published: 30 March 2023
What do parents/carers of children with eczema and young people with eczema think of two websites to help them to manage eczema?
Journal: British Journal of Dermatology (2023)

Journal Article What do parents/carers of children with eczema and young people with eczema think of two websites to help them to manage eczema? Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Page e31, https://doi.org/10.1093/bjd/ljad048 Published: 30 March 2023
The geographical variation of melanoma, basal and squamous cell carcinoma in England
Authors: Anna Ascott, Birgitta van Bodegraven, Sally Vernon, Cate H Orteu, Zoe C Venables
Journal: British Journal of Dermatology (2023)

Skin cancer rates are increasing worldwide due to ageing populations, sun-seeking behaviours and increasing rates of immunosuppression. Understanding the regional variation in skin cancer is vital to planning healthcare services, prevention and screening strategies. Our objective was to report the regional incidence of the three most common types of skin cancer in England: basal cell carcinoma, cutaneous squamous cell carcinoma and melanoma.
Factors associated with mental illness in adults with atopic eczema or psoriasis
Journal: British Journal of Dermatology (2023)

Journal Article Factors associated with mental illness in adults with atopic eczema or psoriasis Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Page e27, https://doi.org/10.1093/bjd/ljad046 Published: 30 March 2023
Use of proton pump inhibitors in people taking BRAF/MEK inhibitors for metastatic melanoma
Journal: British Journal of Dermatology (2023)

Journal Article Use of proton pump inhibitors in people taking BRAF/MEK inhibitors for metastatic melanoma Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Page e29, https://doi.org/10.1093/bjd/ljad047 Published: 30 March 2023
Sugemalimab Monotherapy for Patients With Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma (GEMSTONE-201): Results From a Single-Arm, Multicenter, Phase II Study
Authors: Huiqiang Huang, Rong Tao, Siguo Hao, Yu Yang, Hong Cen, Hui Zhou, Ye Guo, Liqun Zou, Junning Cao, Yunhong Huang, Jie Jin, Liling Zhang, Haiyan Yang, Xiaojing Xing, Huilai Zhang, Yanyan Liu, Kaiyang Ding, Qinzhou Qi, Xiaoli Zhu, Dan Zhu, Siyuan Wang, Teng Fang, Hangjun Dai, Qingmei Shi, Jason Yang
Journal: Journal of Clinical Oncology (2023)

Relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) is a rare and aggressive type of non-Hodgkin lymphoma with limited treatment options. This phase II study evaluated the efficacy and safety of sugemalimab, an anti-PD-L1 monoclonal antibody, in R/R ENKTL.Eligible patients received sugemalimab 1,200 mg intravenously once every 3 weeks for up to 24 months or until progression, death, or study withdrawal. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Key secondary end points included ORR assessed by the investigators, complete response rate, duration of response, and safety.At the data cutoff (February 23, 2022), 80 patients were enrolled and followed for a median of 18.7 months. At baseline, 54 (67.5%) had stage IV disease and 39 (48.8%) had received ≥2 lines of prior systemic therapy. Independent radiologic review committee-assessed ORR was 44.9% (95% CI, 33.6 to 56.6); 28 (35.9%) patients achieved a complete response and seven (9.0%) achieved a partial response, with a 12-month duration of response rate of 82.5% (95% CI, 62.0 to 92.6). Investigator-assessed ORR was 45.6% (95% CI, 34.3 to 57.2), and 24 (30.4%) patients achieved a complete response. Most treatment-emergent adverse events were grade 1-2 in severity, and grade ≥ 3 events were reported in 32 (40.0%) patients.Sugemalimab showed robust and durable antitumor activity in R/R ENKTL. Treatment was well tolerated with expected safety profile for this drug class.
BJD Reviewers January 2022 - December 2022
Journal: British Journal of Dermatology (2023)

Journal Article BJD Reviewers January 2022 - December 2022 Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Pages 577–582, https://doi.org/10.1093/bjd/ljad066 Published: 30 March 2023
B-cell lymphoma extra-large (Bcl-xL) is a promising drug target in Merkel cell carcinoma
Authors: Kaiji Fan, Nalini Srinivas, Linda Kubat, Jan Gravemeyer, Antje Sucker, Dirk Schadendorf, Thilo Gambichler, Jürgen C Becker
Journal: British Journal of Dermatology (2023)

Merkel cell carcinoma (MCC) is an aggressive skin tumour with neuroendocrine differentiation. Immunotherapies are effective in the treatment of patients with advanced-stage MCC, but for patients whose tumours cannot be controlled by the immune system, alternative approaches are urgently needed.To identify overexpressed oncogenes as potential drug targets for MCC.NanoString platform, digital droplet polymerase chain reaction (ddPCR) and fluorescence in situ hybridization (FISH) assays were used to determine copy number variations (CNVs); BCL2L1 and PARP1 mRNA expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR), B-cell lymphoma extra-large (Bcl-xL) and poly (ADP-ribose) polymerase 1 (PARP1) protein by immuno-blot. Specific Bcl-xL inhibitors and a PARP1 inhibitor were used alone or in combination to test their antitumour effect.Screening for CNVs in 13 classic Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative MCC cell lines revealed BCL2L1 gains and amplifications, confirmed by ddPCR in 10 cell lines. By ddPCR and FISH, we demonstrated that BCL2L1 gains are present in tumour tissue. BCL2L1 copy number gains were associated with increased Bcl-xL mRNA and protein expression. However, high Bcl-xL expression was not restricted to MCC cells harbouring a BCL2L1 gain/amplification, suggesting additional epigenetic means of regulation. The functional relevance of Bcl-xL in MCC cells was demonstrated by the fact that specific Bcl-xL inhibitors (A1331852 and WEHI-539) led to the induction of apoptosis. Owing to the strong expression and activation of PARP1 in MCC cell lines, we next tested the combination of Bcl-xL inhibitors with the PARP1 inhibitor olaparib, which showed synergistic antitumour effects.Bcl-xL, which is highly expressed in MCC, appears to be an attractive therapeutic target for the treatment of this tumour, especially as the effect of specific Bcl-xL inhibitors is synergistically enhanced by simultaneous PARP inhibition.
Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial)
Authors: Michael J. Morris, Glenn Heller, David W. Hillman, Olivia Bobek, Charles Ryan, Emmanuel S. Antonarakis, Alan H. Bryce, Olwen Hahn, Himisha Beltran, Andrew J. Armstrong, Lawrence Schwartz, Lionel D. Lewis, Jan H. Beumer, Brooke Langevin, Eric C. McGary, Paul T. Mehan, Amir Goldkorn, Bruce J. Roth, Han Xiao, Colleen Watt, Mary-Ellen Taplin, Susan Halabi, Eric J. Small
Journal: Journal of Clinical Oncology (2023)

Enzalutamide and abiraterone both target androgen receptor signaling but via different mechanisms. The mechanism of action of one drug may counteract the resistance pathways of the other. We sought to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting.
Efficacy and Safety of Gefapixant for Refractory or Unexplained Chronic Cough over 52 Weeks
Authors: Surinder S. Birring, Peter V. Dicpinigaitis, Jaclyn A. Smith, Alyn H. Morice, Lorcan P. McGarvey, Ian D. Pavord, Allison Martin Nguyen, Jonathan Schelfhout, Qing Li, Beata Iskold, Stuart A. Green, George Philip, David R. Muccino, Carmen La Rosa
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

have increased sensitivity for classifying voxels close to the 2856 HU threshold (3).However, further investigations into the pathophysiological mechanisms associated with the PRM and DPM classification differences are needed.This study emphasizes that the measurement of fSAD by CT is critically dependent on breathing instructions.A precise assessment of fSAD is crucial for determining early disease etiology (7) and the efficacy of treatments in patients with early stages of COPD as well as in symptomatic smokers without spirometric evidence of obstructive lung disease (8).Therapies that target fSAD have the potential not only to reduce air trapping but also to slow and even reverse the development of COPD.It is recognized that the measurement of fSAD by CT is critically dependent on breathing instructions.Coaching to RV in a clinical setting will require careful training of CT technologists to deliver instructions similar to those delivered in a pulmonary function laboratory.
Autoantibodies Recognizing Specificity Protein 4 <scp>Co‐occur</scp> With Anti–Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis
Authors: Matthew A. Sherman, Katherine Pak, Iago Pinal‐Fernandez, Willy A. Flegel, Ira N. Targoff, Frederick W. Miller, Lisa G. Rider, Andrew L. Mammen
Journal: Arthritis & Rheumatology (2023)

Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated.
Meet the First Authors
Journal: Circulation Research (2023)

After that, Huitong joined the Quertermous Laboratory as a Postdoctoral Researcher and began work on long non-coding RNA involved in smooth muscle cell phenotypic transition, an important process in atherosclerosis.Huitong is interested in the cell fate transition in cardiovascular and heart diseases and is pursuing epigenetic and post-transcriptional mechanisms of regulation in this area.
Ketones and the Heart: Metabolic Principles and Therapeutic Implications
Authors: Timothy R. Matsuura, Patrycja Puchalska, Peter A. Crawford, Daniel P. Kelly
Journal: Circulation Research (2023)

The ketone bodies beta-hydroxybutyrate and acetoacetate are hepatically produced metabolites catabolized in extrahepatic organs. Ketone bodies are a critical cardiac fuel and have diverse roles in the regulation of cellular processes such as metabolism, inflammation, and cellular crosstalk in multiple organs that mediate disease. This review focuses on the role of cardiac ketone metabolism in health and disease with an emphasis on the therapeutic potential of ketosis as a treatment for heart failure (HF). Cardiac metabolic reprogramming, characterized by diminished mitochondrial oxidative metabolism, contributes to cardiac dysfunction and pathologic remodeling during the development of HF. Growing evidence supports an adaptive role for ketone metabolism in HF to promote normal cardiac function and attenuate disease progression. Enhanced cardiac ketone utilization during HF is mediated by increased availability due to systemic ketosis and a cardiac autonomous upregulation of ketolytic enzymes. Therapeutic strategies designed to restore high-capacity fuel metabolism in the heart show promise to address fuel metabolic deficits that underpin the progression of HF. However, the mechanisms involved in the beneficial effects of ketone bodies in HF have yet to be defined and represent important future lines of inquiry. In addition to use as an energy substrate for cardiac mitochondrial oxidation, ketone bodies modulate myocardial utilization of glucose and fatty acids, two vital energy substrates that regulate cardiac function and hypertrophy. The salutary effects of ketone bodies during HF may also include extra-cardiac roles in modulating immune responses, reducing fibrosis, and promoting angiogenesis and vasodilation. Additional pleotropic signaling properties of beta-hydroxybutyrate and AcAc are discussed including epigenetic regulation and protection against oxidative stress. Evidence for the benefit and feasibility of therapeutic ketosis is examined in preclinical and clinical studies. Finally, ongoing clinical trials are reviewed for perspective on translation of ketone therapeutics for the treatment of HF.
In this Issue
Journal: Circulation Research (2023)

Discovery of Trans-Acting Long Non-Coding RNAs that Regulate Smooth Muscle Cell Phenotype (p 795) Shi et al identify long non-coding RNAs that regulate a phenotype switch in smooth muscle cells.Vascular smooth muscle cells (VSMCs) are a major contributing cell type in the progression of coronary artery disease (CAD) and become pathological by transitioning into a highly proliferative and migratory state.In searching for factors that regulate this transition-which could thus reveal ways to stop it-Shi and colleagues focused on the potential role of long noncoding RNAs (lncRNAs), many of which are regulatory in nature.Human coronary artery SMCs (HCASMCs) were subjected to various CAD stimuli and the expression changes of lncRNAs were analyzed.From the many differentially expressed lncRNAs, the team focused on two-ZIP-POR and TNS1-AS2, which were downand up-regulated respectively relative to unstimulated cells.Interestingly, functional analysis of these two revealed that, despite being differently affected by CAD stimuli, repression of either led to similar effects in HCASMCs-increased migration and proliferation and increased expression of ZEB2, a master regulator of SMC phenotype transition.Both ZIPPOR and TNS1-AS2 were also found to interact directly with the ZEB2 protein to suppress its expression.While it is not known if these lncRNAs influence CAD progression, their suppression of SMC transition suggests such investigations are warranted.
Maternal Anti‐Ro Antibody Titers Obtained With Commercially Available Immunoassays Are Strongly Associated With Immune‐Mediated Fetal Heart Disease
Authors: Edgar Jaeggi, Vathany Kulasingam, Jack Chen, Chun‐Po Steve Fan, Carl Laskin, Robert M. Hamilton, Linda T. Hiraki, Earl D. Silverman, Lusia Sepiashvili
Journal: Arthritis & Rheumatology (2023)

Anti-Ro antibody-positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti-Ro antibody titers and fetal CNL.Antibody-positive mothers referred since 2018 for fetal echocardiography at risk of CNL (group 1; n = 240) or with CNL (group 2; n = 18) were included. Maternal antibody titers were measured with a chemiluminescent immunoassay (CIA). Additional testing on diluted serum samples was used to quantify anti-Ro 60 antibody titers above the analytical measuring range (AMR) of the standard CIA (≥1,375 chemiluminescent units [CU]).Among 27 total mothers with a fetal diagnosis of CNL, all displayed anti-Ro 60 antibody titers that exceeded the AMR of the CIA at least 10-fold. Of 122 mothers in group 1 who underwent additional anti-Ro 60 antibody testing, event rates of CNL (n = 9) were 0% (0 of 45) among mothers with anti-Ro 60 antibody titers from 1,375-10,000 CU, 5% (3 of 56) among mothers with titers from 10,000-50,000 CU, but 29% (6 of 21) among mothers with titers >50,000 CU (odds ratio 13.1, P = 0.0008). Of mothers in group 2 with a primary diagnosis of CNL, 0% (0 of 18 mothers) had anti-Ro 60 antibody titers <10,000 CU, 44% (8 of 18 mothers) had titers from 10,000-50,000 CU, and 56% (10 of 18 mothers) had titers >50,000 CU.CNL is associated with substantially higher anti-Ro antibody titers than are obtained using a standard CIA. Enhancing the assay measuring range allows an improved specificity of identifying pregnancies at risk of CNL.
It is better to light a candle than to curse the darkness: single-cell transcriptomics sheds new light on pancreas biology and disease
Authors: Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E DelGiorno
Journal: Gut (2023)

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis for designing new therapeutic strategies. Here, we review the recent literature on how single-cell transcriptomic approaches have changed our understanding of pancreas biology and disease progression.
Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials
Authors: Andrew Blauvelt, Jacob P Thyssen, Emma Guttman-Yassky, Thomas Bieber, Esther Serra-Baldrich, Eric Simpson, David Rosmarin, Hany Elmaraghy, Eric Meskimen, Chitra R Natalie, Zhuqing Liu, Chenjia Xu, Evangeline Pierce, MaryAnn Morgan-Cox, Esther Garcia Gil, Jonathan I Silverberg
Journal: British Journal of Dermatology (2023)

Abstract Background Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. Objectives To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Methods Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator’s Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. Results After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. Conclusions After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.
Continuous glucose monitoring versus blood glucose monitoring for risk of severe hypoglycaemia and diabetic ketoacidosis in children, adolescents, and young adults with type 1 diabetes: a population-based study
Authors: Beate Karges, Sascha R Tittel, Alexander Bey, Clemens Freiberg, Christof Klinkert, Olga Kordonouri, Susanne Thiele-Schmitz, Carmen Schröder, Claudia Steigleder-Schweiger, Reinhard W Holl
Journal: The Lancet Diabetes & Endocrinology (2023)
Surface charge adaptive nitric oxide nanogenerator for enhanced photothermal eradication of drug-resistant biofilm infections
Authors: Huifang Ma, Yizhang Tang, Fan Rong, Kun Wang, Tengjiao Wang, Peng Li
Journal: Bioactive Materials (2023)

Due to protection of extracellular polymeric substances, the therapeutic efficiency of conventional antimicrobial agents is often impeded by their poor infiltration and accumulation in biofilm. Herein, one type of surface charge adaptable nitric oxide (NO) nanogenerator was developed for biofilm permeation, retention and eradication. This nanogenerator (PDG@Au-NO/PBAM) is composed of a core-shell structure: thermo-sensitive NO donor conjugated AuNPs on cationic poly(dopamine-co-glucosamine) nanoparticle (PDG@Au-NO) served as core, and anionic phenylboronic acid-acryloylmorpholine (PBAM) copolymer was employed as a shell. The NO nanogenerator featured long circulation and good biocompatibility. Once the nanogenerator reached acidic biofilm, its surface charge would be switched to positive after shell dissociation and cationic core exposure, which was conducive for the nanogenerator to infiltrate and accumulate in the depth of biofilm. In addition, the nanogenerator could sustainably generate NO to disturb the integrity of biofilm at physiological temperature, then generate hyperthermia and explosive NO release upon NIR irradiation to efficiently eradicate drug-resistant bacteria biofilm. Such rational design offers a promising approach for developing nanosystems against biofilm-associated infections.
Needle-based confocal laser endomicroscopy for cystic lymphangiomas of the pancreas: the first case series
Authors: Claire Michoud, Tawfik Khoury, Andrea Lisotti, Rodica Gincul, Sarah Leblanc, Anne-Isabelle Lemaistre, Bertrand Napoléon
Journal: Endoscopy (2023)

Cystic lymphangiomas of the pancreas (CLP) were first described by Koch in 1913 [1]. The origin of these benign lesions is not well defined; they could either be congenital malformations or secondary to a lymphatic vessel obstruction due to either radiotherapy, surgery, infection, or trauma [2]. The main challenge in pancreatic cystic lesions (PCLs) is the diagnostic certainty [3]. Needle-based confocal laser endomicroscopy (nCLE), described in pancreatic diseases in 2011 [4], is a very specific technique for the diagnosis of the main PCL [5]. The first description of the identifiable structures by nCLE in CLP is proposed below.
Endoscopic submucosal dissection of a quasi-circumferential lesion of the ileo-cecal valve by using a novel adjustable traction device
Authors: Jean Grimaldi, Louis-Jean Masgnaux, Timothée Wallenhorst, Romain Legros, Jérémie Jacques, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2023)

The technique of submucosal dissection has been expanding rapidly for several years thanks to numerous technical advances. One of these major advances is the improvement of traction strategies, and in particular the appearance of the multi-traction technique. However, several locations remain challenging because of their anatomical particularities, especially lesions of the ileo-cecal valve, which have been the subject of the development of different strategies in recent years [1] [2].